This project is designed to better delineate the pathology of B cell differentiation and function in two malignancies of immuoglobulin (Ig) synthesizing cells, multiple myeloma (MM) and chronic lymphocytic leukemia (CLL). The specific cellular immunoregulatory mechanisms of T cells, functionally and phenotypically defined T cell subsets, null cells and monocyte/macrophages will be examined with respect to proliferation, differentiation and function of malignant cells and their precursors in comparison with normal differentiation. Although many basic observations in this area have already been made, our approach in this prosposal is novel and likely to provide additional new information in a number of areas. Included in these areas of study are T cell regulation of idiotypic Ig production and idiotypic cellular interactions in man; null cell differentiation, function, and null cell suppression of B cell function; T cell subset regulation of autologous mixed lymphocyte responses in myeloma and CLL; and examination of inducer, suppressor and cytotoxic human T cell subset function in these malignancies. In this latter area of investigation we will compare T gamma and T mu subsets with the overlapping but distinct T cell subsets defined by monoclonal antibodies generously provided by Dr. Gideon Goldstein of Ortho Pharmaceutic Corp., and with inducer and suppressor subsets defined functionally in our own laboratory by sensitivity to the in vitro active metabolites of cyclophosphamide in collaboration with Dr. Michael Colvin of Johns Hopkins University.